肿瘤遗传异质性

尽管大多数自发性肿瘤源于单细胞, 但人们逐渐认识到个体肿瘤的内部存在异质性, 这种差异涉及分化程度、细胞增殖率、侵袭和转移能力及治疗反应等众多方面。分子生物学研究也证实肿瘤演进过程中不断产生新的突变, 为肿瘤内部存在异质性增加了更有力的佐证。文章综述了关于肿瘤遗传异质性研究的主要进展。鉴于遗传异质性分析可为揭示肿瘤细胞的产生、扩散、转移的时间段提供重要信息, 文章以瘤内异质性为主线, 列举了遗传异质性存在的实验依据; 阐述了遗传多样性在人类个体肿瘤发展进化史中的研究价值; 介绍了遗传异质性产生的两种模式, 包括肿瘤干细胞模型和克隆进化模型; 总结了遗传异质性在肿瘤转移、治疗中的重要临床意义。文章最后展示了常用的遗传异质性的研究方法, 包括特定基因的分析方法和基于基因组水平的方法, 并对各自的优缺点进行了分析。     

Roles of cAMP and cAMP-dependent protein kinase in the progression of prostate cancer: Cross-talk with the androgen receptor

Prostate carcinomas are among the most frequently diagnosed and death causing cancers affecting males in the developed world. It has become clear that the molecular mechanisms that drive the differentiation of normal prostate cells towards neoplasia involve multiple signal transduction cascades that often overlap and interact. A critical mediator of cellular proliferation and differentiation in various cells (and cancers) is the cAMP-dependent protein kinase, also known as protein kinase A (PKA), and its activating secondary messenger, cAMP. PKA and cAMP have been shown to play critical roles in prostate carcinogenesis and are the subject of this review. In particular we will focus on the cross-talk between PKA/cAMP signaling and that of the androgen receptor.     

肥大细胞及类胰蛋白酶在人甲状腺肿瘤组织中的表达 及其与微血管密度的关系

目的:探讨肥大细胞(mast cell,MC)及类胰蛋白酶(tryptase)与甲状腺肿瘤微血管密度(microvessel density,MVD)的相关性及其对甲状腺癌发生发展的影响。方法:采用甲苯胺蓝组织化学染色和PV免疫组织化学染色对116例甲状腺癌、56例甲状腺腺瘤和10例正常甲状腺组织中MC和tryptase及其CD31的表达进行了检测;对MC和tryptase与MVD的关系进行了统计学分析。结果:甲状腺肿瘤中MC的数量和tryptase阳性表达高于正常甲状腺,而且与肿瘤的类型有关(P<0.01);Spearman等级相关分析显示各组甲状腺组织MC数量和tryptase表达与MVD呈正相关(r=0.900,r=0.636,P<0.05)。结论:MC及其分泌的tryptase有促进血管新生的作用,因而可促进甲状腺肿瘤的浸润和转移。     

区域效应－一个前列腺癌早期诊断的新思路

目前临床上有许多怀疑前列腺癌但穿刺阴性的病例,为了避免漏诊,多数患者必须接受重复穿刺。尽管部分患者经重复穿刺确诊为前列腺癌,而更多患者经过长期随访以及反复穿刺最终确诊为良性病变。近期研究证实,癌灶附近的组织学表现正常的组织中也可发生与癌灶相似的分子改变。因此,我们认为在前列腺癌的发生过程中存在区域效应。在这一理论指导下,选择适当的可反映前列腺癌区域效应的标记物,在穿刺阴性的标本中检出与癌灶相似的分子改变,就可以帮助临床医生在常规病理诊断之前,提前预测前列腺癌的发生。如果能够找到这样的标记物,并在大规模的诊断试验中证实其可行性,那么就可以极大地改善前列腺癌诊断的现状。     

BRD7单核苷酸多态性及鼻咽癌易感性分析

为了探讨BRD7基因的遗传变异在鼻咽癌发生的作用,采用PCR-SSCP和直接测序方法对BRD7 基因的编码区进行单核苷酸多态性（coding-region single nucleotide polymorphism, cSNP）分析,并对两个鼻咽癌家系的高危成员、57个散发性鼻咽癌病人和50个正常人进行了BRD7等位基因分型.在BRD7基因的编码区发现了3个cSNP（C450T、A538C和A737G）,其中A538C颠换导致其编码蛋白的第162个氨基酸由Asp变为Ala;C450T改变与同义的A737C多态性偶联发生在87.7%的鼻咽癌活检组织和配对的外周血、所有的鼻咽癌家系的患者及8个易感成员,但是仅存在于22%的正常人血标本中.C450T多态性变化可以导致其编码蛋白在第133位氨基酸的翻译终止（G133Ter）.以上结果说明,C450T和A737C偶联的多态性改变是鼻咽癌发生和发展的重要遗传易感风险因子之一（P＜0.01）;BRD7基因有两种翻译方式,G133Ter可以导致另一种截断的翻译本（truncated isoform）.     

Morphine addiction and withdrawal alters brain peptide concentrations

This study demonstrates that, during morphine addiction and withdrawal in rats profound alterations in the concentrations of a variety of brain peptides occur. Somatostatin, cholecystokinin, neurotensin and substance P concentrations increased during morphine addiction. Naloxone-induced withdrawal decreased brain concentrations of TRH, somatostatin, neurotensin and substance P. Naloxone alone decreased thalamic substance P and neurotensin concentrations. Vasoactive intestinal peptide concentrations were unaltered by any of the treatments. The fall in the tissue concentration of somatostatin during naloxone-induced withdrawal correlated well with the fall in the circulating growth hormone, suggesting that this could be secondary to somatostatin release. Our data support the hypothesis that brain peptides, acting locally in the brain as neuromodulators, play an important role in the genesis of the syndromes of morphine addiction and withdrawal.     

AEBP1在结直肠癌中的表达及其意义

目的:研究脂肪细胞增强结合蛋白1(AEBP1)在结直肠癌组织中的表达情况,以探索其临床意义。方法:运用免疫组织化学和实时定量PCR技术,对AEBP1在结直肠癌中的表达情况进行检测,并分析其表达量与患者临床病理特征的关系。结果:AEBP1在结直肠正常组织、腺瘤和癌组织中的免疫评分有明显差异(P0.05),而且AEBP1的阳性表达与肿瘤的分期和浸润深度明显相关。基因水平AEBP1的表达在肿瘤组织中明显高于正常组织。结论:AEBP1在结直肠癌组织中存在异常表达,并且可能是结直肠癌早期诊断和浸润深度的肿瘤标志物。     

A Model System for the Study of the Release of Luteinizing Hormone-Releasing Hormone from Isolated Storage Granules

Abstract: We have developed an in vitro system for the study of the release of luteinizing hormone-releasing hormone (LH-RH) from its storage granules. In this system, homogenates of hypothalamic tissue are subjected to hypoosmotic shock, and the LH-RH-containing granules are isolated by means of differential centrifugation. The isolated granules are then incubated in a buffered medium, and the incubation is terminated by passing the incubation mixture through LH-RH affinity columns. The LH-RH associated with the granules passes freely through the columns, whereas the LH-RH released into the medium binds to the columns and is subsequently eluted with an acid solution. LH-RH is quantified by radioimmunoassay (RIA). We tested the effects of various concentrations of KCl on LH-RH release, which was found to be dependent on the concentration of KCl in the medium over the range 40–160 mM. We then studied the effects of pH on the release of LH-RH. Incubation of granules at pH 7.8 in the presence of 160 mM-KC1 resulted in the release from the granules of 14% of the stored LH-RH, whereas incubation at pH 6.2 resulted in the release of approximately 30% of the LH-RH. In addition, granules were incubated at pH 7.8 with MgATP and KCl. MgATP elicited a marked release of LH-RH that was approximately twice that seen in the absence of MgATP. In summary, in this in vitro system, granules containing LH-RH are stable under defined biochemical conditions, and LH-RH release from these granules is stimulated by ions and MgATP.